General synthetic approaches to an important new class of naturally occurring antibiotics and antitumor compounds, the aromatic C-clycosides, will be developed. No unified synthetic approach to aromatic C-glycosides exists. Few of these compounds have been synthesized, and even fewer have been synthesized in a practical manner. The essence of our two complementary approaches consists of coupling an aromatic precursor with an activated glycosyl derivative. This approach is expected to be general, convergent, efficient, and will afford optically pure products. One synthetic method will involve initial O-glycosidation of the phenolic aglycones of these antitumor antibiotics, followed by a novel ortho O to C glycosyl migration. The resulting o-hydroxyphenyl C-glycoside fragment occurs frequently in nature. This potentially valuable reaction, which appears to mimic the biosynthesis of aromatic C-glysocides, has not been applied to their synthesis. A second approach, complementary to the first, involves reaction of a glycosyl halide with an aromatic organometallic reagent, prepared either from an aromatic halide or by ortho metalation of an aromatic ether. Results previously obtained in this laboratory suggest that this reaction can be quite efficient with the proper organometallic reagent. The required equatorial (beta) C-glycoside is known to be the strongly favored product of equilibration. The synthetic objectives of this proposal are seven recently discovered aromatic C-glycoside antitumor compounds and antibiotics. Specifically we propose to synthesize the resorcinol antifungal antibiotic papulacandin D, several members of a class of nontoxic naphthol antitumor antibiotics including toromycin, chrysomycin, ravidomycin, and gilvocaroin, the xanthone C-glycoside mangiferin, the benzoquinone sarubricin A, the naphthoquinone griseusin A, and the anthraquinones vineomycin and nogalamycin. All of these compounds possess significant biological activity and none have been synthesized in satisfactory manner. Our goal is the development of a practical syntheses of these antitumor antibiotics.